The long-term goal of this project is to develop a safe, cost-effective, off-the-shelf, and well characterized bone filler material based on plastics derived from blood plasma. Over 800,000 bone procedures are performed in the US per year, and with the aging US population, this number will only continue to grow. However, current materials, including autografts (e.g. demineralized bone matrix (DBM)), allografts, and engineered biomaterials, all fall short of clinical expectations for reasons such as cost, disease transmission concerns, bone donation issues and complications, and lack of well characterized and consistently performing products. Blood plasma-based plastics have the potential to overcome these limitations. In Phase I Carmell Therapeutics demonstrated that blood plasma-based plastics are biocompatible, biodegradable, bioactive, and form bone in a mouse calvarial defect model. In Phase II Carmell seeks to develop a putty-form of its plastic and obtain safety and efficacy data for use in a premarket approval application to the FDA. To achieve this, the putty will be designed to have similar physical properties to those of DBM-based putties while maintaining the biocompatibility and bioactivity properties of the original blood plasma-based plastic. An accompanying putty delivery device will also be developed. The osteoinductive potential of the product will be tested in a rat muscle-pocket heterotopic bone model. The ability of the product to repair a rabbit long bone radial defect will also be tested in a large, statistical study. Finally, a battery of biological tests will be performed to satisfy FDA- mandated ISO 10993 standards for the biological evaluation of medical devices. PUBLIC HEALTH RELEVANCE: The aging population coupled with the general population's increased activity has raised demand for effective bone graft materials. Current clinical materials fall short of many of the expectations of clinicians for reasons such as inconsistent outcomes, inadequate supply, and cost. Carmell Therapeutics has developed a material made from human blood byproducts that has the potential to be a safe, cost-effective, off-the-shelf, and consistent bone graft therapy.